The overall goal for the project is to study the detailed mechanisms of uronate isomerase and adenosyl- cobyric acid synthetase. Uronate isomerase has been identified as a member of the amidohydrolase superfamily, in which most members catalyze hydrolysis reactions. The reaction of uronate isomerase differs from other family members in that it catalyzes the isomerization of glucuronic and galacturonic acid to fructuronic and tagaturonic acid, respectively. The existence of an isomerase in the amidohydrolase superfamily provides an excellent example of divergent evolution of enzyme function. The modifications to the active site that enables an isomerization reaction in this superfamily are of significant interest. Adenosyl- cobyric acid synthetase (CbiP) catalyzes the sequential amidation of carboxylate groups b, d, e, and g of adenosyl-cobyrinic acid a,c-diamide. The mechanism of CbiP is interesting because it catalyzes chemical reactions at multiple sites within the same substrate. Preliminary data suggest that the amidation of these carboxylate groups is ordered and dissociative. The specific order of amidation and the structural basis for this selectivity will be elucidated. [unreadable] [unreadable]